EMLA cream, a “eutectic mixture of local anesthetics”, was
developed in the early 1980s by Astra Pharmaceutical Production. The
mixture of anesthetics containing lidocaine, prilocaine, and water is liquid at
room temperature, which is partly due to the eutectic equilibrium between
prilocaine and lidocaine at 293 K, as was clear from the start. However, the
full thermodynamic background for the stability of the liquid and its
emulsion-like appearance has never been elucidated. In the present ...

EMLA cream, a “eutectic mixture of local anesthetics”, was
developed in the early 1980s by Astra Pharmaceutical Production. The
mixture of anesthetics containing lidocaine, prilocaine, and water is liquid at
room temperature, which is partly due to the eutectic equilibrium between
prilocaine and lidocaine at 293 K, as was clear from the start. However, the
full thermodynamic background for the stability of the liquid and its
emulsion-like appearance has never been elucidated. In the present study of
the binary system prilocaine-water, a region of liquid-liquid demixing has been observed, linked to a monotectic equilibrium at
302.4 K. It results in a prilocaine-rich liquid containing approximately 0.7 mol fraction of anesthetic. Similar behavior has been
reported for the binary system lidocaine-water (Ce´olin, R.; et al. J. Pharm. Sci. 2010, 99 (6), 2756-2765). In the ternary mixture,
the combination of the monotectic equilibrium and the above-mentioned eutectic equilibrium between prilocaine and lidocaine
results in an anesthetic-rich liquid that remains stable below room temperature. This liquid forms an emulsion-like mixture in the
presence of an aqueous solution saturated with anesthetics. Physical properties and the crystal structure of prilocaine are also
reported.
EMLA cream, a “eutectic mixture of local anesthetics”, was
developed in the early 1980s by Astra Pharmaceutical Production. The
mixture of anesthetics containing lidocaine, prilocaine, and water is liquid at
room temperature, which is partly due to the eutectic equilibrium between
prilocaine and lidocaine at 293 K, as was clear from the start. However, the
full thermodynamic background for the stability of the liquid and its
emulsion-like appearance has never been elucidated. In the present study of
the binary system prilocaine−water, a region of liquid−liquid demixing has been observed, linked to a monotectic equilibrium at
302.4 K. It results in a prilocaine-rich liquid containing approximately 0.7 mol fraction of anesthetic. Similar behavior has been
reported for the binary system lidocaine−water (Céolin, R.; et al. J. Pharm. Sci. 2010, 99 (6), 2756−2765). In the ternary mixture,
the combination of the monotectic equilibrium and the above-mentioned eutectic equilibrium between prilocaine and lidocaine
results in an anesthetic-rich liquid that remains stable below room temperature. This liquid forms an emulsion-like mixture in the
presence of an aqueous solution saturated with anesthetics. Physical properties and the crystal structure of prilocaine are also
reported.